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NIH Awards $1.9 Million to Study the Genetics of MS

The Benaroya Research Institute in Seattle, Wash. has received a grant to study certain white blood cells and areas of the human genome that control their expression.

Could our genes hold the key to unlocking the mystery of
multiple sclerosis? The National Institutes of Health (NIH) is betting
on it. They have awarded a $1.9 million grant to Benaroya Research Institute
(BRI) at Virginia Mason Medical Center to look for changes that take
place at the molecular level in immune cells responsible for the damage
caused by multiple sclerosis (MS).

The co-principal
investigators are Steve Ziegler, Ph.D., a member of BRI and Director of
the Immunology Research Program, and Estelle Bettelli, Ph.D., an
assistant member of BRI.

“We want to understand the factors that make these cells target the spinal cord and brain to cause disease," said Bettelli in a press release.
Bettelli and other scientists have identified different types of T
cells, which they believe induce MS and other autoimmune diseases. She
has also developed system models to study different forms of multiple
sclerosis.

"This work highlights a key mechanism for
understanding and modifying the immune cells that cause autoimmune
diseases like MS," said BRI Director Gerald Nepom, M.D., Ph.D., in the
press release. "It is an exciting example of the power of merging new
genomic technologies with state-of-the-art immunology research to
address a major clinical need."

Biobank: A Wealth of Information

The
researchers will study samples from BRI’s Multiple Sclerosis and
Healthy Control Biorepositories. A biorepository, or biobank, contains
blood and tissue samples collected from people with a specific
condition, as well as samples from healthy volunteers.

“Biorepositories
are used to better understand the biomarkers associated with the
progression of these diseases and identify targets for new therapies,"
explained Ziegler and Bettelli in an interview with Healthline. "BRI is
unique in having such a rich and broad group of biorepositories for our
research.”

The scientists will isolate white blood
cells called CD4+ T cells, which are thought to cause and exacerbate MS.
They will use a technology called DNase hypersensitive site analysis to
map regulatory regions in the genome, which is a person's complete set
of genetic information, consisting of 23 pairs of chromosomes.

“These
regulatory regions control the expression of genes in specific cell
types," Ziegler and Bettelli said. "For the studies in this grant, we’re
testing the hypothesis that these regulatory regions will be different
in the same cell types in individuals with MS as compared to healthy
individuals, and that these differences will drive the inappropriate
expression of certain genes in MS patients.”

A Whole New Perspective

Researchers
are optimistic that the knowledge gleaned in this study might give
scientists a new perspective on MS. Knowing when and where these immune
cells are formed in the body is key to learning how to rein in their
harmful behavior.

“The understanding of how and which
cell populations of the immune system participate in the autoimmune
attack is very important for determining current treatments and
designing new therapeutics tailored to the different forms of MS," said
Bettelli in the press release. "We hope to find ways to significantly
inhibit these dangerous cells with new targeted medicines with fewer
side effects.”

“In addition," the investigators said,
"mapping these regulatory regions may also be useful as a diagnostic
tool, especially in the context of tracking the response to therapeutic
intervention.”

Even with progress being made to
diagnose MS more quickly with magnetic resonance imaging (MRI) scans,
patients who suffer a variety of odd symptoms often go from doctor to
doctor getting conflicting diagnoses. The first step in treating the
disease is to accurately diagnose it as early as possible so that
therapy can have the best chance of staving off disease progression.

Even
after diagnosis, it is often a process of elimination to find the one
disease modifying therapy (DMT) that is most effective for a given
patient, while subjecting them to the fewest side effects.

The
results of this research could not only help diagnose MS sooner but
also pair a patient with a therapy that is genetically matched to their
needs for the most effective results.

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